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Biomedical subjects

T Sun

Publications and source records attributed to T Sun.

At least 73 records · Page 4Linked to original sources
PubMed2000

DNA repair is activated in early stages of p53-induced apoptosis.

p53 is a complex molecule involved in apoptosis, cell cycle arrest, and DNA repair. Since apoptosis may play an important role in deletion of neoplastic cells, an understanding of the mechanism of p53-induced apoptosis may be critical for possible future therapeutic interventions. Recent evidence suggests that p53-induced apoptosis may involve members of the nucleotide excision repair (NER) family, linking these two cellular events. Our work using a temperature-sensitive p53 construct further analyzes p53-induced apoptosis in cultured murine mammary epithelial cells and also suggests that DNA repair plays a role in that process. Although p21 is induced in our system, apoptosis occurs without a detectable preceding G1 cell cycle arrest and independent of cellular alterations brought on by the temperature shift. In addition, clonogenic assays suggest that early stages of p53-induced apoptosis may be reversible upon removal of the apoptosis stimulus. As a possible explanation for this reversibility, our results show that general DNA repair activity increases early in p53-induced apoptosis. We also show that caspase-3 is activated at a timepoint when colony formation begins to drop, suggesting a possible mechanism for the point of no return in p53-induced apoptosis.

Amino Acid Substitution↗
PubMed2000

Cancer skills laboratories for medical students: a promising approach for cancer education.

BACKGROUND: Most medical students graduate without the skills necessary to assist patients in cancer control. To address this problem, the authors developed a cancer skills laboratory for second-year medical students. METHODS: The skills laboratory consists of two hours of training, with 15 minutes allotted per station (six to eight students assigned per station). Faculty and fellows lead the stations on prostate cancer, breast cancer, colorectal cancer, skin cancer, counseling for smoking cessation, and a discussion of anti-tobacco advertisements. Students completed pre- and post-laboratory surveys consisting of ten brief questions. RESULTS: Overall, 94% of eligible students in 1997 and 1998 completed the surveys. Using a five-point scale, self-rated skill level increased from 2.12 to 3.83 when all modalities were averaged (p < .001). CONCLUSIONS: Cancer skills laboratories are a promising new means for cancer education.

Boston↗
PubMed2000

Brainstem-evoked muscle potentials: their prognostic value in experimental spinal cord injury in the rat.

Recording myoelectric motor-evoked potentials is frequently used as an in vivo evaluation technique in experimental studies of spinal cord injury (SCI). The aim of the present study was to determine whether specific neuronal pathways conduct these potentials. Stainless steel screws were permanently implanted into the cranium of 18 rats for stimulation of brainstem-evoked muscle potentials (B-MPs). Twelve rats were subjected to spinal cord lesions that restricted the continuity of the spinal cord to different discrete sections of the lateral and/or ventral white matter (WM) of the left hemicord. Sham rats (n = 6) were subjected to laminectomy only. Left hind limb B-MPs and motor function (open field walking test) were recorded before surgery and weekly thereafter for six consecutive weeks. Motor function was severely affected by SCI in all rats but recovered significantly during the first 14 postoperative days. The degree of functional recovery depended not only on the amount of spared WM but also on the particular section of WM that had been spared. In contrast, B-MP amplitudes also were severely reduced by SCI, but did not recover during the survival period. Moreover, B-MP amplitudes correlated only weakly with the amount of sparedWM and were not influenced by which section ofWM had been spared. While functional recovery correlated significantly with the amount of spared WM, no correlation was found between B-MP amplitudes and functional recovery. B-MP conduction velocities were not affected by SCI. It is therefore believed that B-MPs have little prognostic value for experimental studies of SCI in the rat.

Analysis of Variance↗
PubMed2000

Nitric oxide and atrial natriuretic factor stimulate cGMP-dependent membrane insertion of aquaporin 2 in renal epithelial cells.

In collecting duct principal cells, aquaporin 2 (AQP2) is shuttled from intracellular vesicles to the plasma membrane upon vasopressin (VP) stimulation. VP activates adenylyl cyclase, increases intracellular cAMP, activating protein kinase A (PKA) to phosphorylate AQP2 on the COOH-terminal residue, serine 256. Using rat kidney slices and LLC-PK1 cells stably expressing AQP2 (LLC-AQP2 cells), we now show that AQP2 trafficking can be stimulated by cAMP-independent pathways. In these systems, the nitric oxide (NO) donors sodium nitroprusside (SNP) and NONOate and the NO synthase substrate L-arginine mimicked the effect of VP, stimulating relocation of AQP2 from cytoplasmic vesicles to the plasma membrane. Unlike VP, these other agents did not increase intracellular cAMP. However, SNP increased intracellular cGMP, and exogenous cGMP stimulated AQP2-membrane insertion. Atrial natriuretic factor, which signals via cGMP, also stimulated AQP2 translocation. The VP and SNP effects were blocked by the kinase inhibitor H89. SNP did not stimulate membrane insertion of AQP2 in LLC-PK1 cells expressing the phosphorylation-deficient mutant 256SerAla-AQP2, indicating that phosphorylation of Ser256 is required for signaling. Both PKA and cGMP-dependent protein kinase G phosphorylated AQP2 on this COOH-terminal residue in vitro. These results demonstrate a novel, cAMP-independent and cGMP-dependent pathway for AQP2 membrane insertion in renal epithelial cells.

Amino Acid Sequence↗
PubMed2000

A human YAC transgene rescues craniofacial and neural tube development in PDGFRalpha knockout mice and uncovers a role for PDGFRalpha in prenatal lung growth.

The platelet-derived growth factor alpha-receptor (PDGFRalpha) plays a vital role in the development of vertebrate embryos, since mice lacking PDGFRalpha die in mid-gestation. PDGFRalpha is expressed in several types of migratory progenitor cells in the embryo including cranial neural crest cells, lung smooth muscle progenitors and oligodendrocyte progenitors. To study PDGFRalpha gene regulation and function during development, we generated transgenic mice by pronuclear injection of a 380 kb yeast artificial chromosome (YAC) containing the human PDGFRalpha gene. The YAC transgene was expressed in neural crest cells, rescued the profound craniofacial abnormalities and spina bifida observed in PDGFRalpha knockout mice and prolonged survival until birth. The ultimate cause of death was respiratory failure due to a defect in lung growth, stemming from failure of the transgene to be expressed correctly in lung smooth muscle progenitors. However, the YAC transgene was expressed faithfully in oligodendrocyte progenitors, which was not previously observed with plasmid-based transgenes containing only upstream PDGFRalpha control sequences. Our data illustrate the complexity of PDGFRalpha genetic control, provide clues to the location of critical regulatory elements and reveal a requirement for PDGF signalling in prenatal lung growth, which is distinct from the known requirement in postnatal alveogenesis. In addition, we found that the YAC transgene did not prolong survival of Patch mutant mice, indicating that genetic defects outside the PDGFRalpha locus contribute to the early embryonic lethality of Patch mice.

Animals↗
PubMed2000

Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development.

Little is known about gene action in the preimplantation events that initiate mammalian development. Based on cDNA collections made from each stage from egg to blastocyst, 25438 3'-ESTs were derived, and represent 9718 genes, half of them novel. Thus, a considerable fraction of mammalian genes is dedicated to embryonic expression. This study reveals profound changes in gene expression that include the transient induction of transcripts at each stage. These results raise the possibility that development is driven by the action of a series of stage-specific expressed genes. The new genes, 798 of them placed on the mouse genetic map, provide entry points for analyses of human and mouse developmental disorders.

Animals↗
PubMed2000

Effect of intrathecal morphine and electro-acupuncture on cellular immune function of rats and increment of mu-opioid receptor mRNA expression in PAG following intrathecal morphine.

The present study was to investigate the dynamic changes of cellular immune function of rats with intrathecal injection of (ith) morphine and the regulatory effect of electroacupuncture(EA) stimulation on "Zusanli" (St.36) and "Lanwei" (Extra 37) points. The results showed that ConA-induced rat spleen lymphocyte proliferation was significantly decreased on 2h, 4h, 8h, 12h, 24h, 48h after ith morphine(40microg/50microL). The proliferative response was recovered to nearly normal on 72h. EA on corresponding periods could prevent the decrease of lymphocyte proliferative response of rats induced by ith morphine. The same tendency was observed on the induction of IL-2 production. Further study continued to explore the mechanism of the potentiating effect of mu-opioid receptor in periaqueductal gray (PAG) and hippocampus on the immunosuppression induced by ith morphine at molecular level with in situ hybridization histochemistry technique. The results showed that ith morphine could increase the expression of mu-opioid receptor mRNA.

Analgesics, Opioid↗
PubMed2000

[Comparison of physiological characteristics of different ecotype plants].

Studies on the responses of photosynthesis, leaf water content and stoma resistance of 4 different ecotype plants to water stresses showed that their mechanism of drought-resistance was different. Mesic plants limited water loss from transpiration by increasing their stoma resistance, while xeric plants decreased water loss by keeping the high concentration of cell protoplasm. The latter had a higher efficiency of keeping water than the former. The leaf water content and stoma resistance was decreased from mesic to xeric plants, while the net photosynthetic rate per unit leaf was increased, indicating the difference of physiological characteristics among different ecotype plants.

Photosynthesis↗
PubMed2000

[Current situation of pollution eco-chemistry and its prospects].

As a new discipline, pollution eco-chemistry comes into being with the development and intersection of ecology and environmental chemistry. Main contents of the subject were summarized: 1) movement and transformation of chemical pollutants and their microcosmically eco-chemical processes; 2) ecological effects, eco-toxicology and ecological risk assessment of chemical pollutants; 3) ecological chemistry of global changes; 4) analyses and monitoring of chemical pollutants in ecosystems; 5) eco-chemistry for pollution control. Under the guidance of knowledge innovation as its scientific goal, the research on pollution eco-chemistry will be devoted to a theoretical breakthrough. While doing a through basic research, we should pay attention to related applied research, in order to implement the technological and practical goal of the discipline.

Chemical Phenomena↗
PubMed2000

Role of protein tyrosine kinase in IL-1 beta induced activation of mitogen-activated protein kinase in fibroblast-like synoviocytes of rheumatoid arthritis.

OBJECTIVES: To study mitogen-activated protein kinase (MAPKs) activation in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) under the stimulation of IL-1 beta, and to elucidate the role of protein tyrosine kinase (PTK) in the activation of MAPKs. METHODS: Primary cultures of RA FLS were used. Western blot was applied to examine transient changes in protein tyrosine phosphorylation status and MAPKs activation in RA FLS stimulated with IL-1 beta at various doses, and over different periods. Genistein, the specific PTK inhibitor, was used to evaluate the inhibitory role in activation of MAPKs by IL-1 beta. RESULTS: IL-1 beta transiently increased protein tyrosine phosphorylation, and activated the MAPKs cascades (mainly ERK2, JNK2 and P38) in RA FLS. There was no obvious difference in MAPKs activation among different doses of IL-1 beta (1 IU/ml, 10 IU/ml, 100 IU/ml), but the peak activation of ERK2, JNK2 and P38 took place at 5 min, 15 min and 1 min, respectively, after stimulation with IL-1 beta. The activation of ERK2 was inhibited by genistein, but the inhibitory role on that of JNK and P38 was relatively weak. CONCLUSIONS: During signal transduction of IL-1 beta in RA FLS, tyrosine phosphorylation was increased transiently, the MAPKs cascade was activated in a few minutes, and there was heterogenicity in the activation among three subfamily members. PTK had a role in the activation of ERK, but had weak effects on that of JNK and P38.

Arthritis, Rheumatoid↗
PubMed2000

Therapeutic strategy in the management of stage II-IV epithelial ovarian carcinoma.

OBJECTIVE: To investigate the optimal time of debulking in stage/II to stage IV epithelial ovarian carcinoma, considering corresponding advantages of both surgery and chemotherapy. METHODS: From January 1989 to December 1996, ninety-five stage II to stage IV ovarian cancer patients were treated under two different regimens. Group A-76 cases (2 cases in IIa stage, 4 cases in IIb stage, 6 cases in IIc stage, 58 cases in IIIc stage and 7 cases in IV stage) was managed according to a traditional surgery-chemotherapy regimen; and group B-19 cases (17 cases in IIIc stage and 2 cases in IV stage) was managed with a chemotherapy-surgery-chemotherapy regimen. RESULTS: The optimal debulking rate (no macroscopic residual or residual < 2 cm) in group A was significantly lower than in group B, being 32.9% (25/76) and 68.4% (13/19), respectively (P < 0.001). The average survival time of those with a residual focus > 2 cm was shorter than those with a residual focus < 2 cm, in both groups. Sixteen out of the 51 patients with a residual focus > 2 cm had a second debulking operation, among whom 7 had preoperative chemotherapy. All of these 7 patients had either no residuals or residual < 2 cm. In 9 cases without preoperative chemotherapy, the residuals were all > 2 cm. The average survival time among these two groups were significantly different (P < 0.01). CONCLUSION: (1) For those patients in whom optimal debulking was clinically assessed to be possible, timely operation is mandatory. (2) For those inoperable advanced cases, chemotherapy-surgery-chemotherapy regimen is recommended. (3) For those with residuals > 2 cm and were assessed to be difficult to eradicate during second-look operation, multi-route chemotherapy (intro-arterial, intraperitoneal, and systematic) should be given before going on the second debulking operation. Positive attitude and proper regimen would offer better results. (4) A multicenter prospective study would give more decisive conclusion.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[The significance and characteristics of the gene expressions of c-fos and c-jun in hypertrophic scar and chronic ulcer tissues].

OBJECTIVE: To explore the characteristics and regularity of the expression of c-fos and c-jun genes in hypertrophic scar and chronic ulcer tissues and their relationship to different tissue restoration. METHODS: Tissue samples of hypertrophic scars were harvested from 16 cases of patients after burns and chronic cutaneous ulcers during operation together with the normal skin (n = 5) of the same patients as control. ABC method was employed to detect the gene expression of both c- fos and c-jun in above samples. RESULTS: The positive expression of c-fos and c-jun gene was found in epithelial basal cells and some subcutaneous fibroblasts in normal skin. But the expression of c-jun was weaker than that of c-fos in above tissues. A strong positive expression of c-fos and c-jun genes was found mainly in fibroblasts in the hypertrophic scar. But the combined expression of both tumor genes was most often found in the capillary endothelium, some inflammatory cells and the cytoplasm of fibroblasts in ulcer tissue. CONCLUSION: The results indicated that the amount and location of the expression of c-fos and c-jun genes were different in the three kinds of tissues, suggesting that these two tumor genes may play important roles in wound healing modulation.

Adult↗
PubMed2000

[Purification of prothrombin in Nitschmann fraction III by membrane radial column ion-exchange liquid chromatography].

A method is described for the purification of human prothrombin complex concentrate (PCC) from Nitschmann fraction III by membrane radial column ion-exchange chromatography, which allows large sample volumes to be processed at low operation pressure. The Nitschmann fraction III (15 g) was mixed with 1,000 mL 0.06 mol/L Tris-HCl(pH 7.5). The centrifuged supernatant(10,000 r/min, 15 min, 20 degrees C) was applied onto a DEAE ion-exchange liquid chromatographic column(XK-16 DEAE fast flow Sepharose and DEAE membrane radical column chromatography) with almost the same excellent separation efficiency. The parameters of sample flow rate, elution flow rate and sample capacity were optimized.

Blood Coagulation Factors↗
PubMed1999

Suppression of tumorigenicity in human ovarian cancer cell lines is controlled by a 2 cM fragment in chromosomal region 6q24-q25.

Multiple distinct regions of chromosome 6 are frequently affected by losses of heterozygosity in primary human ovarian carcinomas. We introduced a normal human chromosome 6 into HEY and SKOV-3 ovarian carcinoma cell lines using microcell-mediated chromosome transfer techniques to further investigate the role of this chromosome in ovarian tumorigenesis. The exogenous chromosome was stably propagated in the recipient cells based on fluorescence in situ hybridization (FISH) analyses with a chromosome 6 painting probe. The tumorigenicity of HEY and SKOV-3 cells was completely suppressed after transfer of chromosome 6, but not after transfer of a chromosome 11q13-qter fragment used as control. Using 46 polymorphic microsatellite markers, the region bounded by D6S1649 and D6S1564 was found to be commonly deleted in HEY: chromosome 6 tumorigenic revertant clones. The boundaries of the commonly deleted region could be further narrowed down to a 2 cM (based on the Whitehead genetic map) or 0.36 megabase (based on gdb mapping data) region between D6S1637 and D6S1564 after transferring the exogenous chromosome from revertants into mouse L cells and performing allelic deletion mapping studies against this mouse background. We conclude that this region contains a tumor suppressor gene important for the control of ovarian tumor development.

Animals↗
PubMed1999

Signal joint formation is inhibited in murine scid preB cells and fibroblasts in substrates with homopolymeric coding ends.

During B and T lymphocyte development, immunoglobulin and T cell receptor genes are assembled from the germline V, (D) and J gene segments (Lewis, S.M., 1994. The mechanism of V(D)J joining: lessons from molecular, immunological and comparative analyses. Adv. Immunol. 56, 27-150). These DNA rearrangements, responsible for immune system diversity, are mediated by a site specific recombination machinery via recognition signal sequences (RSSs) composed of conserved heptamers and nonamers separated by spacers of 12 or 23 nucleotides (Lewis, S.M., 1994. The mechanism of V(D)J joining: lessons from molecular, immunological and comparative analyses. Adv. Immunol. 56, 27-150). Recombination occurs only between a RSS with a 12mer spacer and a RSS with a 23mer spacer (Lewis, S.M., 1994. The mechanism of V(D)J joining: lessons from molecular, immunological and comparative analyses. Adv. Immunol. 56, 27-150). RAG1 and RAG2 proteins cleave precisely at the RSS-coding sequence border leading to flush signal ends and coding ends with a hairpin structure (Eastman, M., Leu, T., Schatz, D., 1996. Initiation of V(D)J recombination in vitro obeying the 12/23 rule. Nature 380, 85-88; Roth, D.B., Menetski, J.P., Nakajima, P.B., Bosma, M.J., Gellert, M., 1992. V(D)J recombination: broken DNA molecules with covalently sealed (hairpin) coding ends in scid mouse thymocytes. Cell 983-991: Roth, D.B., Zhu, C., Gellert. M., 1993. Characterization of broken DNA molecules associated with V(D)J recombination. Proc. Natl. Acad. Sci. USA 90, 10,788-10,792; van Gent, D., McBlane, J.. Sadofsky, M., Hesse, J., Gellert, M., 1995. Initiation of V(D)J recombination in a cell-free system. Cell 81, 925-934). Signal ends join, forming a signal joint. The hairpin coding ends are opened by a yet unknown endonuclease, and are further processed to form the coding joint (Lewis, S.M., 1994. The mechanism of V(D)J joining: lessons from molecular, immunological and comparative analyses. Ad. Immunol. 56, 27-150.) The murine scid mutation has been shown to affect coding joints, but much less signal joint formation. In this study we demonstrate that the murine scid mutation inhibits correct signal joint formation when both coding ends contain homopolymeric sequences. We suggest that this finding may be due to the function of the SCID protein as an assembly component in V(D)J recombination.

Animals↗